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| Name | Class |
|---|---|
| Covance | INDUSTRY |
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This is a First in Human (FIH), double-blind, randomised, placebo-controlled study designed to evaluate safety, tolerability and pharmacokinetics (PK) of single and multiple ascending oral doses of AM1476 in healthy subjects.
Part A (SAD); In the SAD part of the study, single oral doses of AM1476 will be administered in up to 9 sequential groups, each consisting of 8 subjects randomised to receive either AM1476 or placebo in a 3:1 ratio. The first 2 subjects in each group will be dosed in a sentinel fashion, 1 subject will receive AM1476 and the other will receive placebo as randomised.
Part B (MAD); The MAD part of the study will explore multiple ascending dosing of AM1476 for 10 days. AM1476 will be administered in up to 6 sequential groups, each consisting of 8 subjects randomised to receive either AM1476 or placebo in a 3:1 ratio.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part A, Group 1: AM1476 1 mg | Experimental | Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state |
|
| Part A, Group 2: AM1476 5 mg | Experimental | Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state |
|
| Part A, Group 3: AM1476 25 mg | Experimental | Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state |
|
| Part A, Group 4: AM1476 125 mg | Experimental | Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state |
|
| Part A, Group 5: AM1476 375 mg | Experimental | Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state |
|
| Part A, Group 6: AM1476 650 mg | Experimental |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| AM1476 | Drug | AM1476 Capsules |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events | A treatment-emergent adverse-event (TEAE) was defined as an adverse event that started during or after first dosing, or started prior to first dosing and increased in severity after first dosing. | Through study completion, an average of 7 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Cmax | maximum plasma concentration | From pre-dose to up to 48 hours post-dose |
| Cmax | maximum plasma concentration | Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose. |
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Inclusion Criteria:
Exclusion Criteria
Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, haematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the Investigator (or designee).
History of significant hypersensitivity, intolerance, or allergy to any drug compound, food, or other substance, unless approved by the Investigator (or designee).
History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair will be allowed).
Any of the following observed in at least 2 of 3 ECG measurements performed:
Any history of additional risk factors for torsades de pointes (eg, heart failure, hypokalaemia, family history of long QT syndrome).
Any history or current controlled or uncontrolled hypertension or systolic blood pressure > 140 mmHg or diastolic blood pressure > 90 mmHg confirmed by repeat measurement.
History of alcoholism or drug/chemical abuse within 2 years prior to Check-in (Day -1).
Alcohol consumption of > 21 units per week for males and > 14 units per week for females. One unit of alcohol equals ½ pint (285 mL) of beer or lager, 1 glass (125 mL) of wine, or 1/6 gill (25 mL) of spirits.
Positive alcohol breath test result or positive urine drug screen (confirmed by repeat) at Screening or Check-in (Day -1).
Positive hepatitis panel and/or positive human immunodeficiency virus test (Appendix 2).
Participation in a clinical study involving administration of an investigational drug (new chemical entity) in the past 90 days prior to dosing.
Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's Wort, within 30 days prior to dosing, unless deemed acceptable by the Investigator (or designee).
Use or intend to use any prescription medications/products other than hormone replacement therapy, oral, implantable, transdermal, injectable, or intrauterine contraceptives within 14 days prior to dosing, unless deemed acceptable by the Investigator (or designee).
Use or intend to use slow release medications/products considered to still be active within 14 days prior to Check-in (Day -1), unless deemed acceptable by the Investigator (or designee).
Use or intend to use any non-prescription medications/products including vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations within 7 days prior to Check-in (Day -1), unless deemed acceptable by the Investigator (or designee).
Use of tobacco- or nicotine-containing products within 3 months prior to Check-in (Day -1) or positive cotinine at Screening or Check-in (Day -1).
Ingestion of poppy seeds, Seville orange, or grapefruit-containing foods or beverages within 7 days prior to Check-in (Day -1).
Subjects who are vegetarians, vegans, or are unable to consume the high-fat breakfast (subjects who will participate in a food-effect evaluation only).
Receipt of blood products within 2 months prior to Check-in (Day -1).
Donation of blood from 3 months prior to Screening, plasma from 2 weeks prior to Screening, or platelets from 6 weeks prior to Screening.
Poor peripheral venous access.
Have previously completed or withdrawn from this study or any other study investigating AM1476, and have previously received AM1476.
Subjects who are not willing to minimise or avoid exposure to natural or artificial sunlight (tanning beds or UVA/B treatment) following administration of study drug until 2 weeks after the last dose.
Subjects who, in the opinion of the Investigator (or designee), should not participate in this study.
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Covance Clinical Research Unit | Leeds | LS2 9LH | United Kingdom |
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| ID | Title | Description |
|---|---|---|
| FG000 | Part A, Groups 1 to 9: Placebo | Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules |
| FG001 | Part A, Group 1: AM1476 1 mg | Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules |
| FG002 | Part A, Group 2: AM1476 5 mg | Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| FG003 | Part A, Group 3: AM1476 25 mg | Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| FG004 | Part A, Group 4: AM1476 125 mg | Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| FG005 | Part A, Group 5: AM1476 375 mg | Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| FG006 | Part A, Group 6: AM1476 650 mg | Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| FG007 | Part A, Group 7: AM1476 950 mg | Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| FG008 | Part A, Group 8: AM1476 1500 mg | Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| FG009 | Part A, Group 9: AM1476 2400 mg | Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| FG010 | Part B, Groups 1 to 3: Placebo | Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules |
| FG011 | Part B, Group 1: AM1476 100 mg QD | Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules |
| FG012 | Part B, Group 2: AM1476 375 mg BID | Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules |
| FG013 | Part B, Group 3: AM1476 500 mg BID | Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Part A, Groups 1 to 9: Placebo | Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules |
| BG001 | Part A, Group 1: AM1476 1 mg |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Treatment-Emergent Adverse Events | A treatment-emergent adverse-event (TEAE) was defined as an adverse event that started during or after first dosing, or started prior to first dosing and increased in severity after first dosing. | The safety analysis set included all participants who received at least 1 dose of study drug. | Posted | Count of Participants | Participants | Through study completion, an average of 7 weeks |
|
Through study completion, an average of 7 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Part A, Groups 1 to 9: Placebo | Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state Placebo: Placebo Capsules |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Palpitations | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Chief Medical Officer | AnaMar AB | +46 (0)46-275 60 00 | info@anamar.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 6, 2021 | May 15, 2023 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | May 17, 2021 | May 15, 2023 | SAP_001.pdf |
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Part A (SAD) Within each group, subjects will be randomised in a 3:1 ratio to receive either AM1476 (n=6) or placebo (n=2). The first 2 subjects in each group will be dosed in a sentinel fashion; 1 subject will receive AM1476 and the other will receive placebo as randomised.
Part B (MAD) Within each group, subjects will be randomised in a 3:1 ratio to receive either AM1476 (n=6) or placebo (n=2).
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Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state
|
| Part A, Group 7: AM1476 950 mg | Experimental | Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state |
|
| Part A, Group 8: AM1476 1500 mg | Experimental | Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state |
|
| Part A, Group 9: AM1476 2400 mg | Experimental | Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state |
|
| Part A, Groups 1 to 9: Placebo | Placebo Comparator | Part A, Groups 1 to 9: AM1476 placebo-matching capsule, orally once on Days 1 in fasted state |
|
| Part B, Group 1: AM1476 100 mg QD (once daily) | Experimental | Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state |
|
| Part B, Group 2: AM1476 375 mg BID (twice daily) | Experimental | Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state |
|
| Part B, Group 3: AM1476 500 mg BID | Experimental | Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state |
|
| Part B, Groups 1 to 3: Placebo | Placebo Comparator | Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state |
|
| Placebo | Drug | Placebo Capsules |
|
| Tmax | time to Cmax | From pre-dose to up to 48 hours post-dose |
| Tmax | time to Cmax | Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose. |
| T½ | terminal half-life | From pre-dose to up to 48 hours post-dose |
| T½ | terminal half-life | Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose. |
| AUC0-tlast | area under the curve from time 0 to time of the last quantifiable concentration | From pre-dose to up to 48 hours post-dose |
| AUC0-tau | area under the curve over a dosing interval (tau) | Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose. |
| CL/F | apparent total clearance | From pre-dose to up to 48 hours post-dose |
| CL/F | apparent total clearance | Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose. |
| Vz/F | apparent volume of distribution during the terminal phase | From pre-dose to up to 48 hours post-dose |
| Vz/F | apparent volume of distribution during the terminal phase | Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose. |
Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state
AM1476: AM1476 Capsules
| BG002 | Part A, Group 2: AM1476 5 mg | Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| BG003 | Part A, Group 3: AM1476 25 mg | Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| BG004 | Part A, Group 4: AM1476 125 mg | Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| BG005 | Part A, Group 5: AM1476 375 mg | Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| BG006 | Part A, Group 6: AM1476 650 mg | Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| BG007 | Part A, Group 7: AM1476 950 mg | Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| BG008 | Part A, Group 8: AM1476 1500 mg | Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| BG009 | Part A, Group 9: AM1476 2400 mg | Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| BG010 | Part B, Groups 1 to 3: Placebo | Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules |
| BG011 | Part B, Group 1: AM1476 100 mg QD | Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules |
| BG012 | Part B, Group 2: AM1476 375 mg BID | Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules |
| BG013 | Part B, Group 3: AM1476 500 mg BID | Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules |
| BG014 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Height | Mean | Standard Deviation | cm |
|
| Body Weight | Mean | Standard Deviation | kg |
|
| Body Mass Index | Mean | Standard Deviation | kg/m2 |
|
Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state
AM1476: AM1476 Capsules
| OG002 | Part A, Group 2: AM1476 5 mg | Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| OG003 | Part A, Group 3: AM1476 25 mg | Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| OG004 | Part A, Group 4: AM1476 125 mg | Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| OG005 | Part A, Group 5: AM1476 375 mg | Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| OG006 | Part A, Group 6: AM1476 650 mg | Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| OG007 | Part A, Group 7: AM1476 950 mg | Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| OG008 | Part A, Group 8: AM1476 1500 mg | Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| OG009 | Part A, Group 9: AM1476 2400 mg | Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules |
| OG010 | Part B, Groups 1 to 3: Placebo | Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules |
| OG011 | Part B, Group 1: AM1476 100 mg QD | Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules |
| OG012 | Part B, Group 2: AM1476 375 mg BID | Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules |
| OG013 | Part B, Group 3: AM1476 500 mg BID | Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules |
|
|
| Secondary | Cmax | maximum plasma concentration | The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476. At the 1 mg AM1476 dose level, the AM1476 concentrations for one participant were below the level of quantification at all timepoints. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | From pre-dose to up to 48 hours post-dose |
|
|
|
| Secondary | Cmax | maximum plasma concentration | The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476 | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose. |
|
|
|
| Secondary | Tmax | time to Cmax | The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476. At the 1 mg AM1476 dose level, the AM1476 concentrations for one participant were below the level of quantification at all timepoints. | Posted | Median | Full Range | hour | From pre-dose to up to 48 hours post-dose |
|
|
|
| Secondary | Tmax | time to Cmax | The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476 | Posted | Median | Full Range | hour | Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose. |
|
|
|
| Secondary | T½ | terminal half-life | The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476. At the 1 mg AM1476 dose level, the t½ was not calculable due to the limited quantifiable AM1476 concentrations available. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour | From pre-dose to up to 48 hours post-dose |
|
|
|
| Secondary | T½ | terminal half-life | The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476. A reliable characterization of the terminal half-life could not be obtained according the calculation criteria in the Statistical analytical plan for 2 participants dosed with 100 mg QD and 1 participant dosed with 375 mg BID on Day 10. | Posted | Geometric Mean | Geometric Coefficient of Variation | hour | Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose. |
|
|
|
| Secondary | AUC0-tlast | area under the curve from time 0 to time of the last quantifiable concentration | The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476. At the 1 mg AM1476 dose level, the AUC was not reported for 4 participants due to less than 3 consecutive quantifiable concentrations (calculation criteria in the Statistical analytical plan). | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | From pre-dose to up to 48 hours post-dose |
|
|
|
| Secondary | AUC0-tau | area under the curve over a dosing interval (tau) | The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476 | Posted | Geometric Mean | Geometric Coefficient of Variation | h*ng/mL | Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose. |
|
|
|
| Secondary | CL/F | apparent total clearance | The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476. At the 1 mg AM1476 dose level, the apparent total clearance was not calculable due to the limited quantifiable AM1476 concentrations available. | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | From pre-dose to up to 48 hours post-dose |
|
|
|
| Secondary | CL/F | apparent total clearance | The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476 | Posted | Geometric Mean | Geometric Coefficient of Variation | L/h | Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose. |
|
|
|
| Secondary | Vz/F | apparent volume of distribution during the terminal phase | The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476. At the 1 mg AM1476 dose level, the apparent volume of distribution during the terminal phase was not calculable due to the limited quantifiable AM1476 concentrations available. | Posted | Geometric Mean | Geometric Coefficient of Variation | L | From pre-dose to up to 48 hours post-dose |
|
|
|
| Secondary | Vz/F | apparent volume of distribution during the terminal phase | The pharmacokinetic (PK) analysis set included all participants who received at least 1 dose of AM1476. A reliable characterization of the apparent volume of distribution during the terminal phase could not be obtained according the calculation criteria in the Statistical analytical plan for 2 participants dosed with 100 mg QD and 1 participant dosed with 375 mg BID on Day 10. | Posted | Geometric Mean | Geometric Coefficient of Variation | L | Day 1: From pre-dose up to 24 hours post first dose after QD dosing and from pre-dose up to 12 hours post first dose after BID dosing. Day 10: From pre-dose up to 48 hours post last dose. |
|
|
|
| 0 |
| 18 |
| 0 |
| 18 |
| 3 |
| 18 |
| EG001 | Part A, Group 1: AM1476 1 mg | Part A, Group 1: AM1476 1 mg capsule, orally once on Day 1 in fasted state AM1476: AM1476 Capsules | 0 | 6 | 0 | 6 | 0 | 6 |
| EG002 | Part A, Group 2: AM1476 5 mg | Part A, Group 2: AM1476 5 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules | 0 | 6 | 0 | 6 | 0 | 6 |
| EG003 | Part A, Group 3: AM1476 25 mg | Part A, Group 3: AM1476 25 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules | 0 | 6 | 0 | 6 | 4 | 6 |
| EG004 | Part A, Group 4: AM1476 125 mg | Part A, Group 4: AM1476 125 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules | 0 | 6 | 0 | 6 | 1 | 6 |
| EG005 | Part A, Group 5: AM1476 375 mg | Part A, Group 5: AM1476 375 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules | 0 | 7 | 0 | 7 | 2 | 7 |
| EG006 | Part A, Group 6: AM1476 650 mg | Part A, Group 6: AM1476 650 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules | 0 | 6 | 0 | 6 | 3 | 6 |
| EG007 | Part A, Group 7: AM1476 950 mg | Part A, Group 7: AM1476 950 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules | 0 | 6 | 0 | 6 | 2 | 6 |
| EG008 | Part A, Group 8: AM1476 1500 mg | Part A, Group 8: AM1476 1500 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules | 0 | 6 | 0 | 6 | 4 | 6 |
| EG009 | Part A, Group 9: AM1476 2400 mg | Part A, Group 9: AM1476 2400 mg capsule, orally once on Days 1 in fasted state AM1476: AM1476 Capsules | 0 | 6 | 0 | 6 | 5 | 6 |
| EG010 | Part B, Groups 1 to 3: Placebo | Part B, Groups 1 to 3: AM1476 placebo-matching capsule, orally once or twice on Days 1-10 in fasted state Placebo: Placebo Capsules | 0 | 6 | 0 | 6 | 6 | 6 |
| EG011 | Part B, Group 1: AM1476 100 mg QD | Part B, Group 1: AM1476 100 mg capsule, orally once on Days 1-10 in fasted state AM1476: AM1476 Capsules | 0 | 6 | 0 | 6 | 3 | 6 |
| EG012 | Part B, Group 2: AM1476 375 mg BID | Part B, Group 2: AM1476 375 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules | 0 | 6 | 0 | 6 | 2 | 6 |
| EG013 | Part B, Group 3: AM1476 500 mg BID | Part B, Group 3: AM1476 500 mg capsule, orally twice on Days 1-9 and once on Days 10 in fasted state AM1476: AM1476 Capsules | 0 | 6 | 0 | 6 | 4 | 6 |
| Ocular discomfort | Eye disorders | MedDRA 23.1 | Systematic Assessment |
|
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Flatulence | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Frequent bowel movements | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Application site erythema | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Application site rash | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Catheter site erythema | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Chest pain | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Thirst | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Vessel puncture site bruise | General disorders | MedDRA 23.1 | Systematic Assessment |
|
| Oral herpes | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| SARS-CoV-2 test positive | Investigations | MedDRA 23.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Muscle twitching | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Depressed level of consciousness | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Dizziness Postural | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Lethargy | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Syncope | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
|
| Nervousness | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
|
| Oropharyngeal discomfort | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
|
| Dermatitis contact | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Petechiae | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
|
| Hot flush | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
|
Not provided
Not provided
| Male |
|
|
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| Day 10 |
|
|
|
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| Day 10 |
|
|